The objectives of the proposed research are to further define the process whereby skeletal muscle adapts to high-resistance (weight-lifting) exercise, and provide a longitudinal time sequence of events for both structural and functional alterations in skeletal muscle during prolonged exercise. Adult cats are operantly conditioned to flex their right wrist against increasing resistance to receive a food reward. This procedure has the advantage of inducing significant hypertrophy in the muscles of one limb, while the muscles of the opposite limb can be used for comparative studies. This exercise regimen has been shown to increase the total number of fibers determined from cross-sectional profiles through the greatest girth of the muscle belly. One mechanism for this increase has been shown to be fiber splitting. In the proposed study, the ultrastructural and histochemical features of muscle fibers that are undergoing division by splitting will be characterized, and the adaptive changes that occur in the exercising muscle that contribute to fiber splitting will be investigated. The effect of prolonged strength training on isozyme forms of myosin and contractile properties of muscle will also be investigated. A study of the effect of prolonged detraining on muscle trained to peak performance will be undertaken. A single myofiber isolation procedure has been developed which will result in a determination of the absolute number of fibers in trained and untrained muscle. This project will also manipulate the androgen status of the exercising cats through castration and administration of commercially available anabolic steroids to determine the effects of altered androgenic/anabolic state on exercise performance and muscle adaptation to weight-training. EMG will be used to assess adaptive changes in the function and recruitment of exercising muscles. The proposed study will further elucidate the dramatic structural and functional alterations that occur in skeletal muscle that is adapting to high-resistance exercise.